Introduction to MedDRA: Coding and Data Analysis · Narrative. Narrative vignette. A 75-year-old...
Transcript of Introduction to MedDRA: Coding and Data Analysis · Narrative. Narrative vignette. A 75-year-old...
Introduction to MedDRA:Coding and Data Analysis
Jane Knight42nd European Cystic Fibrosis Conference5th June 2019
MedDRA Definition
MedDRA is a clinically-validated international medical terminology used by regulatory authorities and the regulated biopharmaceutical industry. The terminology is used through the entire regulatory process, from pre-marketing to post-marketing, and for data entry, retrieval, evaluation, and presentation.
4000281
MedDRA’s Purpose
• Facilitate the exchange of clinical information through standardization
• Important tool for product evaluation, monitoring, communication, electronic records exchange, and oversight
• Supports coding (data entry) and retrieval and analysis of clinical information about human medical products including pharmaceuticals, biologics, vaccines, and drug-device combination products
000281 5
MedDRA Users Profile
6
• As of January 2019–5,700 Subscribing organizations (MSSO+JMO)
–122 Countries• Graph shows types of
subscribing organizations
000281
Scope of MedDRA
8000281
Medical conditionsIndications
Investigations (tests, results)Medical and surgical proceduresMedical, social, family history
Medication errorsProduct quality issuesDevice-related issuesProduct use issues
Pharmacogenetic termsToxicologic issues
Standardized queries
Not a drug dictionary
Not an equipment, device,diagnostic product dictionary
Clinical trial study design terms
Patient demographicterms
Frequency qualifiers
Numerical values forresults
Severity descriptors
INOUT
MedDRA Structure
System Organ Class (SOC) (27)
High Level Group Term (HLGT) (337)
High Level Term (HLT) (1,737)
Preferred Term (PT) (23,708)
Lowest Level Term (LLT) (80,262)
MedDRA Version 22.0000281 9
Examples of Cystic Fibrosis Terms
• Other CF terms include–Gastrointestinal–Hepatic–Pancreatic–CF gene carrier
10
A Multi-Axial Terminology
• Multi-axial = the representation of a medical concept in multiple SOCs–Allows grouping by different classifications–Allows retrieval and presentation via different data sets
• All PTs assigned a primary SOC–Determines which SOC will represent a PT during
cumulative data outputs–Prevents “double counting”–Supports standardized data presentation–Pre-defined allocations should not be changed by users
000281 12
SOC = Respiratory, thoracic andmediastinal disorders(Secondary SOC)
HLGT = Respiratory tract infections
HLT = Viral upper respiratorytract infections
HLT = Influenza viral infections
HLGT = Viral infectious disorders
SOC = Infections and infestations
(Primary SOC)
PT = Influenza
A Multi-Axial Terminology (cont)
000281 13
Rules for Primary SOC Allocation
• PTs represented in only one SOC are automatically assigned that SOC as primary
• PTs for diseases, signs and symptoms are assigned to prime manifestation site SOC
• Congenital and hereditary anomalies terms have SOC Congenital, familial and genetic disorders as Primary SOC
• Neoplasms terms have SOC Neoplasms benign, malignant and unspecified (incl cysts and polyps) as Primary SOC – Exception: Cysts and polyps have prime manifestation
site SOC as Primary SOC• Infections and infestations terms have SOC Infections
and infestations as Primary SOC000281 14
Primary SOC Priority
If a PT links to more than one of the exceptions, the following priority will be used to determine primary SOC:1st: Congenital, familial and genetic disorders2nd: Neoplasms benign, malignant and
unspecified (incl cysts and polyps)3rd: Infections and infestations
000281 15
A Multi-Axial Terminology (cont)
PTs in the following SOCs only appear in that particular SOC and not in others, i.e., they are not multi-axial
• Investigations•Surgical and medical procedures•Social circumstances
000281 16
Can You Select the Primary SOC for This PT?
17000281
PT HLT HLGT SOCCongenital HIV infection
Viral infections congenital
Infections and infestations congenital
Congenital, familial and genetic disorders
Congenital neonatal infections
Neonatal and perinatal conditions
Pregnancy, puerperium and perinatal conditions
Retroviral infections
Viral infectious disorders
Infections and infestations
Acquired immunodeficiency syndromes
Immunodeficiency syndromes
Immune system disorders
MSSO’s MedDRA Browsers
• MedDRA Desktop Browser (MDB)– Download MDB and release files from MedDRA website
• MedDRA Web-Based Browser (WBB)– https://tools.meddra.org/wbb/
• Features– Both require MedDRA ID and password – View/search MedDRA and SMQs– Support for all MedDRA languages– Language specific interface– Ability to export search results and Research Bin to local
file system000281 18
MedDRA Mobile Browser
• MedDRA Mobile Browser for use on phones and tablets
• Accessed at: mmb.meddra.org
• Requires your organisation’s MedDRA ID and Password
20000140
PtC Documents
25
PtC Category PtC Document Purpose Languages Release CycleTerm Selection MedDRA Term Selection:
Points to ConsiderPromote accurate and consistent coding with MedDRA
English and Japanese
Updated with each MedDRA release
MedDRA Term Selection: Points to Consider Condensed Version
Shorter version focusing on general coding principles to promote accurate and consistent use of MedDRA worldwide
All MedDRA languages (except English and Japanese)
Update as needed
Data Retrieval and Presentation
MedDRA Data Retrieval and Presentation: Points to Consider
Demonstrate how data retrieval options impact the accuracy and consistency of data output
English and Japanese
Updated with each MedDRA release
MedDRA Data Retrieval and Presentation: Points to Consider Condensed Version
Shorter version focusing on general retrieval and analysis principles to promote accurate and consistent use of MedDRA worldwide
All MedDRA languages (except English and Japanese)
Update as needed
General MedDRA Points to Consider Companion Document
More detailed information, examples, and guidance on specific topics of regulatory importance. Intended as a “living” document with frequent updates based on users’ needs. First edition covers data quality and medication errors.
English and Japanese
Updated as needed
000281
• Provides term selection advice for industry and regulatory purposes
• Objective is to promote accurate and consistent term selection to facilitate a common understanding of shared data
• Recommended to be used as basis for individual organization’s own coding conventions
MedDRA Term Selection: Points to Consider (MTS:PTC)
26000281
MTS:PTC Points of Note
• In some cases with more than one option for selecting terms, a “preferred option” is identifiedbut this does not limit MedDRA users to applying that option. Organizations should be consistent in their choice of option.
• Section 4.1 – Versioning (Appendix)–4.1.1 Versioning methodologies–4.1.2 Timing of version implementation
000281 27
General Term Selection Principles
• Quality of Source Data• Quality Assurance• Do Not Alter MedDRA• Always Select a Lowest Level Term• Select Only Current Lowest Level Terms• When to Request a Term• Use of Medical Judgment in Term Selection• Selecting More than One Term• Check the Hierarchy• Select Terms for All Reported Information, Do Not
Add Information
28000281
Quality of Source DataQuality Assurance
• Quality of original information impacts quality of output
• Obtain clarification of data• Can be optimized by careful design of data
collection forms and proper training of staff• Organizations’ coding guidelines should be
consistent with MTS:PTC• Review of term selection by qualified individuals• Human oversight of automated coding results
29000281
Do Not Alter MedDRA
• MedDRA is a standardized terminology with a pre-defined term hierarchy
• Users must not make ad hoc structural alterations, including changing the primary SOC allocation
• If terms are incorrectly placed, submit a change request to the MSSO
30000281
Always Select a Lowest Level TermSelect Only Current LLTs
• Lowest Level Term that most accurately reflects the reported verbatim information should be selected
• Degree of specificity may be challenging–Example: “Abscess on face” select “Facial
abscess,” not simply “Abscess”• Select current LLTs only
–Non-current terms for legacy conversion/historical purposes
000281 31
When to Request a TermUse of Medical Judgment
• Avoid company-specific “work-arounds” for MedDRA deficiencies. If concept not adequately represented in MedDRA, submit Change Request to MSSO.
• If no exact match in MedDRA, use medical judgment to match to an existing term that adequately represents the concept
32000281
Selecting More than One TermCheck the Hierarchy
• Can select more than one LLT to represent reported information. Document procedures. –Selecting one term may lead to loss of specificity–Selecting more than one term may lead to redundant
counts• Check the hierarchy above a selected LLT (PT, HLT,
HLGT, SOC) to ensure placement accurately reflects meaning of reported term
33000281
Select Terms for All Reported Information
• Select terms for every AR/AE reported, regardless of causal association
• Select terms for device-related events, product quality issues, medication errors, medical and social history, investigations and indications as appropriate
34000281
Do Not Add Information
• Do not make diagnosis if only signs/symptoms reported
Reported LLT Selected Comment
Abdominal pain, increased serum
amylase, and increased serum lipase
Abdominal pain
It is inappropriate to assign an LLT for
diagnosis of “pancreatitis”
Serum amylase increased
Lipase increased
000281 35
Assessing the Reported Information
• Consider what is being reported. Is it a:– Clinical condition - Diagnosis, sign or symptom?– Indication?– Test result?– Injury?– Procedure?– Medication error?– Product use issue?– Product quality issue?– Social circumstance?– Device issue?– Procedural complication?
– Is it a combination of these?
The type of report will influence the way you search for a suitable LLT. It may indicate in which SOC you expect to find the closest match.
36
Coding Example -Narrative
Narrative vignetteA 75-year-old male receiving Drug X for rheumatoid arthritis developed symptomatic aortic valve stenosis. The patient’s medical history is significant for colon cancer and cigarette smoking. He underwent an aortic valve replacement and developed a sternal wound infection three days post-surgery.
37
Coding Example 2
Symptoms
The patient states she has been experiencing increasingly frequent episodes of coughing
39
Coding Example 4
Medication errors
Patient accidentally took drug Y instead of drug X and became short of breath
41
Coding Example 6
Indications
The patient was prescribed Drug X to preventMycobacterium avium complex lung infection
43
Coding Example 7
Specificity
Following the procedure, the patient experienced several days of constipation
44
Coding Example 8
Surgical and medical procedures
His breathing improved markedly with more regular chest physical therapy
45
Term Selection Points
• Diagnoses and Provisional Diagnoses with or without Signs and Symptoms
• Death and Other Patient Outcomes• Suicide and Self-Harm• Conflicting/Ambiguous/Vague Information• Combination Terms• Age vs. Event Specificity• Body Site vs. Event Specificity• Location-Specific vs. Microorganism-Specific Information• Modification of Pre-existing Conditions• Exposures During Pregnancy and Breast Feeding• Congenital Terms• Neoplasms• Medical and Surgical Procedures• Investigations
47000281
Term Selection Points (cont)
• Medication Errors, Accidental Exposures and Occupational Exposures
• Misuse, Abuse and Addiction• Transmission of Infectious Agent via Product• Overdose, Toxicity and Poisoning• Device-related Terms• Drug Interactions• No Adverse Effect and “Normal” Terms• Unexpected Therapeutic Effect• Modification of Effect• Social Circumstances• Medical and Social History• Indication for Product Use• Off Label Use• Product Quality Issues
48000281
Diagnoses and Provisional Diagnoses
49000281
SINGLE DIAGNOSIS
DEFINITIVE DIAGNOSIS PROVISIONAL DIAGNOSIS
Single diagnosis without signs and symptoms
•Diagnosis (only possible option)
Single provisional diagnosis without signs and symptoms
•Provisional diagnosis (only possible option)
Example: “Myocardial infarction” select “Myocardial infarction”
Example: “Possible myocardial infarction” select “Myocardial infarction” (select term as if definitive diagnosis)
Similar principles apply for multiple diagnoses
Diagnoses and Provisional Diagnoses (cont)
50000281
SINGLE DIAGNOSISDEFINITIVE DIAGNOSIS PROVISIONAL DIAGNOSIS
Single diagnosis with signs/ symptoms
•Preferred: Diagnosis only
Single provisional diagnosis with signs/symptoms
•Preferred: Provisional diagnosis and signs/symptoms
Example: “Anaphylactic reactionwith rash, dyspnoea, hypotension, and laryngospasm” select “Anaphylactic reaction”
Example: “Possible myocardial infarction with chest pain,dyspnoea, diaphoresis” select “Myocardial infarction” “Chest pain”, “Dyspnoea”, and “Diaphoresis”
Similar principles apply for multiple diagnoses
Diagnoses and Provisional Diagnoses (cont)
51000281
SINGLE DIAGNOSISDEFINITIVE DIAGNOSIS PROVISIONAL DIAGNOSIS
Single diagnosis with signs/ symptoms
•Alternate: Diagnosis and signs/symptoms
Single provisional diagnosis with signs/symptoms
•Alternate: Signs/symptoms only (as provisional diagnosis may change
Example: “Anaphylactic reactionwith rash, dyspnoea, hypotension, and laryngospasm” select “Anaphylactic reaction”, “Rash”, “Dyspnoea”, Hypotension”, and “Laryngospasm”
Example: “Possible myocardial infarction with chest pain,dyspnoea, diaphoresis” select “Chest pain”, “Dyspnoea”, and “Diaphoresis”
Similar principles apply for multiple diagnoses
Diagnoses and Provisional Diagnoses (cont)
• Always include signs/symptoms not associated with diagnosis
52000281
Reported LLT Selected
Myocardial infarction, chest pain, dyspnoea, diaphoresis, ECG changes and jaundice
Myocardial infarction Jaundice (note that jaundice is
not typically associated with myocardial infarction)
Micro-organism Specific Infection
• Select term to capture infecting micro-organism at specified site
53000140
Micro-organism Specific Infection
• If no appropriate combination term exists, the preferredapproach is to select two LLTs for both pathogen and site
• The alternate approach is to choose to select only one term
54000140
Conflicting/Ambiguous Information
• First, try to obtain more specific informationReported LLT Selected Comment
Hyperkalaemia with a serum potassium of 1.6
mEq/L
Serum potassium abnormal
LLT Serum potassium abnormal covers both of the reported concepts
(note: serum potassium of 1.6 mEq/L is a low result,
not high)
GU pain Pain
“GU” could be either “genito-urinary” or “gastric
ulcer”. If additional information is not available, then select a term to reflect
the information that is known, i.e., LLT Pain
000281 55
Vague Information
• First, try to obtain more specific information
Reported LLT Selected Comment
Turned green Unevaluable event
“Turned green” reported alone is vague; this could refer to a patient condition or even to a product (e.g.,
pills)
Patient had a medical problem of unclear type
Ill-defined disorder
Since it is known that there is some form of a
medical disorder, LLT Ill-defined disorder can be
selected
000281 56
Combination Terms
• One condition is more specific than the other
• A MedDRA combination term is available
57000281
Reported LLT Selected
Arrhythmia due to atrial fibrillation Atrial fibrillation
Hepatic function disorder (acute hepatitis) Hepatitis acute
Reported LLT Selected
Retinopathy due to diabetes Diabetic retinopathy
Rash with itching Itchy rash
Combination Terms (cont)
• If splitting provides more clinical information, select more than one term
• In all cases of combination terms, apply medical judgment
58000281
Reported LLT Selected
Diarrhoea and vomiting DiarrhoeaVomiting
Wrist fracture due to fall Wrist fractureFall
Investigations
• Medical condition vs. investigation result
Reported LLT Selected Comment
Hypoglycaemia HypoglycaemiaLLT Hypoglycaemia
links to SOC Metabolism and
nutrition disorders
Decreased glucose Glucose decreasedLLT Glucose decreased
links to SOC Investigations
000281 59
Investigations (cont)
• Unambiguous investigation result
• Ambiguous investigation resultReported LLT Selected Comment
His glucose was 40 Glucose abnormal
No units have been reported. Select LLTGlucose abnormal if
clarification cannot be obtained.
Reported LLT Selected Comment
Glucose 40 mg/dL Glucose lowGlucose is clearly
below the reference range
000281 60
Investigations (cont)
• Investigation results consistent with diagnosis
• Grouped investigation result termsReported LLT Selected Comment
Increased alkaline phosphatase,
increased SGPT, increased SGOT and
elevated LDH
Alkaline phosphatase increased
SGPT increasedSGOT increasedLDH increased
Select four individual terms. A single term
such as LLT Liver function tests
abnormal should notbe selected.
Reported LLT Selected CommentElevated potassium, K
7.0 mmol/L, and hyperkalaemia
HyperkalaemiaIt is not necessary to select LLT Potassium
increased
000281 61
Which LLT Would You Select?
Verbatim: “Became color blind in adolescence”
A. Color blindnessB. Blindness colorC. Colour blindness acquiredD. Color blindness acquired
63
Which LLT Would You Select?
Verbatim: “Turned very greasy”
A. Ill-defined disorderB. Unevaluable eventC. Skin greasyD. Unevaluable reaction
64
Which LLT Would You Select?
Verbatim: “Deliberately took an overdose”
A. Intentional overdoseB. Overdose NOSC. Deliberate overdoseD. Overdose
65
Which LLT Would You Select?
Verbatim: “Four-year old accidentally took his mother’s medication”
A. Accidental overdose B. Accidental exposure to product by child C. Accidental drug intake by childD. Accidental ingestion
66
Which LLT Would You Select?
Verbatim: “Infection after surgery”
A. InfectionB. Postoperative wound infection C. Surgical wound infectionD. Postoperative infection
67
Which LLT Would You Select?
Verbatim: “Had GU”
A. Gastric ulcerB. Ill-defined disorderC. GUD. Unevaluable eventE. Genitourinary tract infection
68
Which LLT Would You Select?
Verbatim: “Hypernatraemia (Serum sodium = 115 mEq/L)”
A. Serum sodium abnormalB. HypernatraemiaC. HyponatraemiaD. Serum sodium decreased
69
Which LLT Would You Select?
Verbatim: “Death from multiple organ failure following haemorrhage post lung transplant”
A. Sudden death B. Death C. Multiple organ failureD. Lung transplant
70
Which LLT Would You Select?
Verbatim: “Patient was found dead”
A. Death from natural causesB. Death C. Died in sleep D. Found dead
71
Which LLT Would You Select?
Verbatim: “The hospital diagnosed a perinephric abscess due to Proteus spp.”
A. Proteus infectionB. Perinephric abscessC. Proteus infection AND Perinephric abscessD. Abscess bacterial
72
Which LLT Would You Select?
Verbatim: “Died as a result of a suicide attempt”
A. Suicide gesture B. Attempted suicide C. Completed suicide D. Death
73
Which LLT Would You Select?
Verbatim: “Abused by her father”
A. Physical abuseB. Child sexual abuseC. Child neglectD. Child abuse
74
Which LLT Would You Select?
Verbatim: “After taking OTC NSAIDs, along with his prescribed antibiotic, he developed pain in her kidneys.”
A. Adverse reaction to antibioticsB. Nephrotoxicity C. Kidney painD. Drug interaction
75
• Provides data retrieval and presentation options for industry or regulatory purposes
• Most effective when used in conjunction with MedDRA Term Selection: PTC document
• Recommended to be used as basis for individual organization’s own data retrieval conventions
MedDRA Data Retrieval and Presentation: Points to Consider (DRP:PTC)
76000282
Query Strategy Tips• Define the condition• Develop inclusion/exclusion criteria• Good browser is key component• Search “non multi-axial” and “other/support” SOCs• Search a term’s “neighbors”, including secondary locations• Use grouping terms where applicable• Avoid using LLTs (Exception: species information at LLT
level in SOC Infections and infestations)• Store for future use• Review for impact of new MedDRA versions
78
Complete the Circle (Connect the DOTSSS!)
Diagnosis/disease terms
Operations (Surgical and medical procedures)
Tests (Investigations)
Signs & symptoms
Social circumstances
Support SOCs (Other…)
79
Standardised MedDRA Queries (SMQs)
• Collaboration between CIOMS (Council for International Organizations of Medical Sciences) and ICH (MSSO)
• Groupings of terms from one or more MedDRA SOCs related to medical condition or area of interest
• Terms relate to signs/symptoms, diagnoses, syndromes, physical findings, laboratory and other test data, etc.
• Intended to aid in case identification 000282 80
SMQ Benefits and Limitations
• Benefits– Application across multiple therapeutic areas– Validated reusable search logic– Standardized communication of safety information– Consistent data retrieval– Maintenance by MSSO/JMO
• Limitations– Do not cover all medical topics or safety issues– Will evolve and undergo further refinement even though
they have been tested during development
000282 81
SMQ in Production -Examples
• As of Version 22.0, a total of 104 level 1 SMQs in production• Agranulocytosis• Anaphylactic reaction• Cerebrovascular
disorders• Convulsions• Depression and
suicide/self-injury• Hepatic disorders• Hypersensitivity• Ischaemic heart disease• Lack of efficacy/effect
• Medication errors• Osteonecrosis• Peripheral neuropathy• Pregnancy and neonatal
topics• Pseudomembranous colitis• Rhabdomyolysis/myopathy• Severe cutaneous adverse
reactions• Systemic lupus
erythematosus000282 82
MedDRA Term Inclusion
• SMQs are constructed at MedDRA PT level
• LLTs that are subordinate to an included PT are also included
83000282
Narrow and Broad Searches
• “Narrow” scope – specificity (cases highly likely to be condition of interest)
• “Broad” scope – sensitivity (all possible cases)• “Broad search” = All broad + all narrow terms
000282 84
Narrow vs. Broad Example
85
SMQ Lactic acidosis
000282
Narrow TermsBlood lactic acid increasedHyperlactacidaemiaLactic acidosis
Broad TermsAcid base balance abnormalAcidosisAnion gap abnormalAnion gap increasedBlood alkalinisation therapyBlood bicarbonate abnormalBlood bicarbonate decreasedBlood gases abnormalBlood lactic acid abnormalBlood pH abnormalBlood pH decreasedComa acidoticKussmaul respirationMetabolic acidosisPCO2 abnormalPCO2 decreasedUrine lactic acid increased
Algorithmic SMQs
• Some SMQs are designed to utilize algorithms
• Better case identification among broad search terms may result if cases are selected by a defined combination of selected terms
000282 86
Algorithmic SMQ Example
• Anaphylactic reaction (SMQ):– A case with any of the following PTs:
• Anaphylactic reaction• Anaphylactic shock• Anaphylactic transfusion reaction• Anaphylactoid reaction• Anaphylactoid shock• Circulatory collapse• Dialysis membrane reaction• Kounis syndrome• Procedural shock• Shock• Shock symptom• Type I hypersensitivity(Narrow search terms = Category A)
000282 87
Algorithmic SMQ Example (cont)
• Case = A (Narrow terms) • Or Term from Category B and term from Category C• Or Term from either Category B or Category C
plus Term from Category D
Category B –Upper airway/Respiratory
Category C –Angioedema/Urticaria, etc.
Category D –Cardiovascular/Hypotension
Acute respiratory failure
Allergic oedema Blood pressure decreased
Asthma Angioedema Blood pressure diastolic decreased
Bronchial oedema Erythema Blood pressure systolic decreased
000282 88
Hierarchical SMQs
• Some SMQs may develop as set of queries related to one another in a hierarchical relationship
• Not related to MedDRA standard hierarchy• One or more subordinate SMQs combined
to create a superordinate, more inclusive SMQ
000282 89
Hierarchical SMQ Example
Haematopoietic cytopenias
Haematopoietic cytopenias affecting more than one type
of blood cell
Haematopoietic erythropenia
Haematopoietic leukopenia
Haematopoietic thrombocytopenia
000282 90
MedDRA Training Opportunities – Available for Users
• Free Face-to-Face (F2F) training – Coding with MedDRA– Safety Data Analysis and Standardised MedDRA Queries– Getting Started with MedDRA
• Free webinars – Getting Started with MedDRA– MedDRA Overview– MedDRA Coding Basics– Advanced MedDRA Coding– Data Analysis and Query Building with MedDRA– Standardised MedDRA Queries – What’s New with MedDRA (with each MedDRA release)
92000283
MedDRA Training Opportunities – Available to All
• Free resources on MedDRA website–Slides for all F2F courses and webinars–Short videocasts on MedDRA-related topics
• Available in several languages• Can be downloaded or viewed directly on website• Help trainees prepare for F2F courses
• Webinars and videocasts available on new MedDRA MSSO YouTube Channel
94000283
More Resources for MedDRA Users
• MedDRA website–Help Desk–Subscriptions–News and Events–MedDRA Best Practices document–Points to Consider documents–Terminology downloads–Training–Tools–MedDRA publications–User group meetings–Expert meetings
95000283
MSSO Contacts
• Website–www.meddra.org
• Email–[email protected]
• Frequently Asked Questions–www.meddra.org/faq
96